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Toolkit for cellular studies of mammalian mitochondrial inorganic polyphosphate.
Hambardikar, Vedangi; Akosah, Yaw A; Scoma, Ernest R; Guitart-Mampel, Mariona; Urquiza, Pedro; Da Costa, Renata T; Perez, Matheus M; Riggs, Lindsey M; Patel, Rajesh; Solesio, Maria E.
Afiliación
  • Hambardikar V; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Akosah YA; Department of Molecular Pathobiology, College of Dentistry, New York University, New York City, NY, United States.
  • Scoma ER; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Guitart-Mampel M; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Urquiza P; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Da Costa RT; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Perez MM; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Riggs LM; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
  • Patel R; Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States.
  • Solesio ME; Department of Biology, and Center for Computational and Integrative Biology (CCIB), Rutgers University, Camden, NJ, United States.
Front Cell Dev Biol ; 11: 1302585, 2023.
Article en En | MEDLINE | ID: mdl-38161329
ABSTRACT

Introduction:

Inorganic polyphosphate (polyP) is an ancient polymer which is extremely well-conserved throughout evolution, and found in every studied organism. PolyP is composed of orthophosphates linked together by high-energy bonds, similar to those found in ATP. The metabolism and the functions of polyP in prokaryotes and simple eukaryotes are well understood. However, little is known about its physiological roles in mammalian cells, mostly due to its unknown metabolism and lack of systematic methods and effective models for the study of polyP in these organisms.

Methods:

Here, we present a comprehensive set of genetically modified cellular models to study mammalian polyP. Specifically, we focus our studies on mitochondrial polyP, as previous studies have shown the potent regulatory role of mammalian polyP in the organelle, including bioenergetics, via mechanisms that are not yet fully understood.

Results:

Using SH-SY5Y cells, our results show that the enzymatic depletion of mitochondrial polyP affects the expression of genes involved in the maintenance of mitochondrial physiology, as well as the structure of the organelle. Furthermore, this depletion has deleterious effects on mitochondrial respiration, an effect that is dependent on the length of polyP. Our results also show that the depletion of mammalian polyP in other subcellular locations induces significant changes in gene expression and bioenergetics; as well as that SH-SY5Y cells are not viable when the amount and/or the length of polyP are increased in mitochondria.

Discussion:

Our findings expand on the crucial role of polyP in mammalian mitochondrial physiology and place our cell lines as a valid model to increase our knowledge of both mammalian polyP and mitochondrial physiology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Cell Dev Biol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Cell Dev Biol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza